Faculty Bibliography

[This corrects the article DOI: 10.1186/s43058-020-00027-3.].

Background/UNASSIGNED:Implementation science (IS) has the potential to serve an important role in encouraging the successful uptake of evidence-based interventions. The current state of IS awareness and engagement among health researchers, however, is relatively unknown. Methods/UNASSIGNED:To determine IS awareness and engagement among health researchers, we performed an online survey of health researchers in the USA in 2018. Basic science researchers were excluded from the sample. Engagement in and awareness of IS were measured with multiple questionnaire items that both directly and indirectly ask about IS methods used. Unrecognized IS engagement was defined as participating in research using IS elements and not indicating IS as a research method used. We performed simple logistic regressions and tested multivariable logistic regression models of researcher characteristics as predictors of IS engagement. Results/UNASSIGNED:< 0.001). Conclusion/UNASSIGNED:Overall, awareness of IS is high among health researchers, yet there is also a high prevalence of unrecognized IS engagement. Efforts are needed to further disseminate what constitutes IS research and increase IS awareness among health researchers.

The presence of an extra copy of human chromosome 21 (Hsa21) leads to a constellation of phenotypic manifestations in Down syndrome (DS), including prominent effects on the brain and immune system. Intensive efforts to unravel the molecular mechanisms underlying these phenotypes may help developing effective therapies, both in DS and in the general population. Here we review recent progress in genetic and epigenetic analysis of trisomy 21 (Ts21). New mouse models of DS based on syntenic conservation of segments of the mouse and human chromosomes are starting to clarify the contributions of chromosomal subregions and orthologous genes to specific phenotypes in DS. The expression of genes on Hsa21 is regulated by epigenetic mechanisms, and with recent findings of highly recurrent gene-specific changes in DNA methylation patterns in brain and immune system cells with Ts21, the epigenomics of DS has become an active research area. Here we highlight the value of combining human studies with mouse models for defining DS critical genes and understanding the trans-acting effects of a simple chromosomal aneuploidy on genome-wide epigenetic patterning. These genetic and epigenetic studies are starting to uncover fundamental biological mechanisms, leading to insights that may soon become therapeutically relevant.

BACKGROUND:Early identification of vasospasm prior to symptom onset would allow prevention of delayed cerebral ischemia (DCI) in aneurysmal subarachnoid hemorrhage (aSAH). Dynamic cerebral autoregulation (DCA) is a noninvasive means of assessing cerebral blood flow regulation by determining independence of low-frequency temporal oscillations of systemic blood pressure (BP) and cerebral blood flow velocities (CBFV). METHODS:Eight SAH patients underwent prospectively a median of 7 DCA assessments consisting of continuous measurements of BCFV and BP. Transfer function analysis was applied to calculate average phase shift (PS) in low (0.07-0.2 Hz) frequency range for each hemisphere as continuous measure of DCA. Lower PS indicated poorer regulatory response. DCI was defined as a 2-point decrease in Glasgow Coma Score and/or infarction on CT. RESULTS:Three subjects developed symptomatic vasospasm with median time-to-DCI of 9 days. DCI was significantly associated with lower PS over the entire recording period (Wald = 4.28; p = 0.039). Additionally, there was a significant change in PS over different recording periods after adjusting for DCI (Wald = 15.66; p = 0.001); particularly, a significantly lower mean PS day 3-5 after bleed (14.22 vs 27.51; p = 0.05). CONCLUSIONS:DCA might be useful for early detection of symptomatic vasospasm. A larger cohort study of SAH patients is currently underway.